tbuckley/cabot-search huggingface dataset:
Preexisting Immunity Drives the Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma
Authors: Giuseppina Arbore, Luca Albarello, Gabriele Bucci, Marco Punta, Andrea Cossu, Lorella Fanti, Aurora Maurizio, Francesco Di Mauro, Vito Bilello, Gianluigi Arrigoni, Silvia Bonfiglio, Donatella Biancolini, Francesco Puccetti, Ugo Elmore, Luca Vago, Stefano Cascinu, Giovanni Tonon, Riccardo Rosati, Giulia Casorati, Paolo Dellabona
Journal: Cancer Research (2023)

Current treatment for patients with locally advanced esophageal adenocarcinoma (EAC) is neoadjuvant chemotherapy (nCT), alone or combined with radiotherapy, before surgery. However, fewer than 30% of treated patients show a pathologic complete response to nCT, which correlates with increased 5-year survival compared with nonresponders. Understanding the mechanisms of response to nCT is pivotal to better stratify patients and inform more efficacious therapies. Here, we investigated the immune mechanisms involved in nCT response by multidimensional profiling of pretreatment tumor biopsies and blood from 68 patients with EAC (34 prospectively and 34 retrospectively collected), comparing complete responders versus nonresponders to nCT. At the tumor level, complete response to nCT was associated with molecular signatures of immune response and proliferation, increased putative antitumor tissue-resident memory CD39+ CD103+ CD8+ T cells, and reduced immunosuppressive T regulatory cells (Treg) and M2-like macrophages. Systemically, complete responders showed higher frequencies of immunostimulatory CD14+ CD11c+ HLA-DRhigh cells, and reduced programmed cell death ligand 1-positive (PD-L1+) monocytic myeloid-derived suppressor cells, along with high plasma GM-CSF (proinflammatory) and low IL4, CXCL10, C3a, and C5a (suppressive). Plasma proinflammatory and suppressive cytokines correlated directly and inversely, respectively, with the frequency of tumor-infiltrating CD39+ CD103+ CD8+ T cells. These results suggest that preexisting immunity in baseline tumor drives the clinical activity of nCT in locally advanced EAC. Furthermore, it may be possible to stratify patients based on predictive immune signatures, enabling tailored neoadjuvant and/or adjuvant regimens.Multidimensional profiling of pretreatment esophageal adenocarcinoma shows patient response to nCT is correlated with active preexisting immunity and indicates molecular pathways of resistance that may be targeted to improve clinical outcomes.
Sentiment Analysis of Social Media Users’ Emotional Response to Sudden Cardiac Arrest During a Football Broadcast
Authors: Nino Fijačko, Robert Greif, Gregor Štiglic, Primož Kocbek, Benjamin S. Abella
Journal: JAMA Network Open (2023)

This case series analyzes social media users’ sentiments after successful cardiopulmonary resuscitation of Damar Hamlin following his sudden cardiac arrest on national television.
Comparison of Commercial Negotiated Price and Cash Price Between Physician-Owned Hospitals and Other Hospitals in the Same Hospital Referral Region
Authors: Yang Wang, Elizabeth Plummer, Yuchen Wang, Peter Cram, Ge Bai
Journal: JAMA Network Open (2023)

This cross-sectional study compares commercial negotiated prices and cash prices between physician-owned hospitals and other hospitals in the same hospital referral region (HRR) using price information available through the Hospital Price Transparency Rule.
Concurrent immune checkpoint inhibition and selective immunosuppressive therapy in patients with immune-related enterocolitis
Authors: Yousef R Badran, Fangwen Zou, Sienna M Durbin, Barbara E Dutra, Hamzah Abu-Sbeih, Anusha S Thomas, Mehmet Altan, John A Thompson, Wei Qiao, Donna E Leet, Po-Ying Lai, Nora K Horick, Michael A Postow, David M Faleck, Yinghong Wang, Michael Dougan
Journal: Journal for ImmunoTherapy of Cancer (2023)

Purpose Immune checkpoint inhibitor (ICI) therapy is often suspended because of immune-related enterocolitis (irEC). We examined the effect of resumption of ICIs with or without concurrent selective immunosuppressive therapy (SIT) on rates of symptom recurrence and survival outcomes. Methods This retrospective, multicenter study examined patients who were treated with ICI and developed irEC requiring SIT (infliximab or vedolizumab) for initial symptom control or to facilitate steroid tapering between May 2015 and June 2020. After symptom resolution, patients were restarted either on ICI alone or on concurrent ICI and SIT at the discretion of the treating physicians. The associations between irEC recurrence and treatment group were assessed via univariate analyses and multivariate logistic regression. Cox proportional hazards model was used for survival analysis. Results Of the 138 included patients who required SIT for initial irEC symptom control, 61 (44.2%) patients resumed ICI without concurrent SIT (control group) and 77 (55.8%) patients resumed ICI therapy with concurrent SIT: 33 with infliximab and 44 with vedolizumab. After symptom resolution, patients in the control group were more commonly restarted on a different ICI regimen (65.6%) compared with those receiving SIT (31.2%) (p&lt;0.001). The total number of ICI doses administered after irEC resolution and ICI resumption was similar in both groups (four to five doses). Recurrence of severe colitis or diarrhea after ICI resumption was seen in 34.4% of controls compared with 20.8% of patients receiving concurrent SIT. Concurrent SIT was associated with reduced risk of severe irEC recurrence after ICI resumption in a multivariate logistic regression model (OR 0.34; 95% CI 0.13 to 0.92; p=0.034). There was no difference in survival outcomes between patients in the control group and patients concurrently treated with SIT. Conclusion After resolution of irEC symptoms, reinitiation of ICI with concurrent SIT is safe, reduces severe irEC recurrence, and has no negative impact on survival outcomes.
Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy
Authors: Gang Fan, Feng Cao, Tingting Kuang, Huan Yi, Chengcheng Zhao, Lijie Wang, Jiayan Peng, Zhenhua Zhuang, Tong Xu, Yuting Luo, Yuchen Xie, Hongying Li, Kun Zhang, Yujiao Zeng, Xiyu Zhang, Sihan Peng, Xianliang Qiu, Dongqi Zhou, Huan Liang, Bin Yang, Jian Kang, Ya Liu, Yi Zhang
Journal: Gut Microbes (2023)

Although changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.
Increased intestinal permeability and downregulation of absorptive ion transporters <i>Nhe3</i> , <i>Dra</i> , and <i>Sglt1</i> contribute to diarrhea during <i>Clostridioides difficile</i> infection
Authors: F. Christopher Peritore-Galve, Izumi Kaji, Anna Smith, Lauren M. Walker, John A. Shupe, M. Kay Washington, Holly M. Scott Algood, Pradeep K. Dudeja, James R. Goldenring, D. Borden Lacy
Journal: Gut Microbes (2023)

Background & Aim Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea and pseudomembranous colitis. Two protein toxins, TcdA and TcdB, produced by C. difficile are the major determinants of disease. However, the pathophysiological causes of diarrhea during CDI are not well understood. Here, we investigated the effects of C. difficile toxins on paracellular permeability and apical ion transporters in the context of an acute physiological infection.Methods We studied intestinal permeability and apical membrane transporters in female C57BL/6J mice. Üssing chambers were used to measure paracellular permeability and ion transporter function across the intestinal tract. Infected intestinal tissues were analyzed by immunofluorescence microscopy and RNA-sequencing to uncover mechanisms of transporter dysregulation.Results Intestinal permeability was increased through the size-selective leak pathway in vivo during acute CDI in a 2-day-post infection model. Chloride secretory activity was reduced in the cecum and distal colon during infection by decreased CaCC and CFTR function, respectively. SGLT1 activity was significantly reduced in the cecum and colon, accompanied by ablated SGLT1 expression in colonocytes and increased luminal glucose concentrations. SGLT1 and DRA expression was ablated by either TcdA or TcdB during acute infection, but NHE3 was decreased in a TcdB-dependent manner. The localization of key proteins that link filamentous actin to the ion transporters in the apical plasma membrane was unchanged. However, Sglt1, Nhe3, and Dra were drastically reduced at the transcript level, implicating downregulation of ion transporters in the mechanism of diarrhea during CDI.Conclusions CDI increases intestinal permeability and decreases apical abundance of NHE3, SGLT1, and DRA. This combination likely leads to dysfunctional water and solute absorption in the large bowel, causing osmotic diarrhea. These findings provide insights into the pathophysiological mechanisms underlying diarrhea and may open novel avenues for attenuating CDI-associated diarrhea.
Argon plasma coagulation under direct peroral cholangioscopy for intraductal papillary mucinous neoplasm of the gallbladder
Authors: Kyong Joo Lee, Se Woo Park, Eun Shin, Dong Hee Koh, Jin Lee
Journal: Endoscopy (2023)

A gallbladder intraductal papillary neoplasm, similar to a bile duct and pancreas intraductal papillary mucinous neoplasm (IPMN), is a rare premalignant lesion characterized by superficial spread, dilated gallbladder and bile ducts, and multifocal distribution [1] [2].
Application of rubber band and clip traction for removal of a submucosal fecalith mimicking a submucosal tumor of the appendix under colonoscopy
Authors: Longping Chen, Linfu Zheng, Zhiping Chen, Dazhou Li, Wen Wang
Journal: Endoscopy (2023)

The term "submucosal tumors" generally refers to colorectal uplifted lesions with a complete upper mucosal cortex, including lipomas, stromal tumors, lymphomas, and neuroendocrine tumors [1]. Approximately 13 % of gastrointestinal submucosal tumors are malignant. Endoscopic ultrasonography (EUS) is the first choice of modality for the diagnosis of submucosal tumors [2]. Here we report an unusual case of a submucosal fecalith mimicking a submucosal tumor of the appendix.
SENP1 Decreases RNF168 Phase Separation to Promote DNA Damage Repair and Drug Resistance in Colon Cancer
Authors: Min Wei, Xinping Huang, Liming Liao, Yonglu Tian, Xiaofeng Zheng
Journal: Cancer Research (2023)

The DNA damage response (DDR) is essential for the maintenance of genomic stability. Protein posttranslational modifications play pivotal roles in regulating the DDR process. Here, we found that SUMOylated RNF168 undergoes liquid-liquid phase separation (LLPS), which restricts the recruitment of RNF168 to DNA damage sites, reduces RNF168-catalyzed H2A ubiquitination, restrains 53BP1 in nuclear condensates, and ultimately impairs nonhomologous DNA end joining repair efficiency. Sentrin/SUMO-specific protease 1 (SENP1) was identified as a specific deSUMOylase of RNF168, and it was highly expressed in colorectal adenocarcinoma. In response to DNA damage, SENP1 decreased RNF168 SUMOylation and prevented RNF168 from forming nuclear condensates, thus promoting damage repair efficiency and cancer cell resistance to DNA damaging agents. Moreover, high SENP1 expression correlated with poor prognosis in patients with cancer, and SENP1 depletion sensitized cancer cells to chemotherapy. In summary, these findings reveal DDR is suppressed by SUMOylation-induced LLPS of RNF168 and suggest that SENP1 is a potential target for cancer therapy.Sentrin/SUMO-specific protease 1 decreases RNF168 SUMOylation and liquid-liquid phase separation to promote DNA damage repair, safeguarding genomic integrity and driving chemotherapy resistance.
Errors in Methods, Discussion, and Supplement
Journal: JAMA Network Open (2023)

Jennifer A. Jairam, MSc; Simone N. Vigod, MD, MSc; Arjumand Siddiqi, ScD; Jun Guan, MSc; Alexa Boblitz, MPH; Xuesong Wang, MSc; Patricia O’Campo, PhD; Joel G. Ray, MD, MSc
A Case of Adenomyosis Showing Size Reduction in a Follicular Lymphoma Patient Receiving Chemotherapy With R-Bendamustine
Authors: Minjung Seo, Yoo Jin Lee, Hyung Jin Choi, Jae Cheol Jo, Seol Hoon Park
Journal: Clinical Nuclear Medicine (2023)

Abstract We describe a case of adenomyosis that reduced in size in a patient with lymphoma on receiving chemotherapy. A 48-year-old woman with worsening left flank pain was diagnosed with follicular lymphoma. [ 18 F]FDG PET/CT revealed multiple hypermetabolic lymph nodes in the bilateral cervical, axillary, mediastinal, mesenteric, retroperitoneal, iliac, and inguinal regions. In addition, adenomyosis with mild hypermetabolism was demonstrated on [ 18 F]FDG PET/CT. The size and metabolism of adenomyosis decreased after chemotherapy with R-bendamustine; in addition, along with decrease in estradiol levels, the patient experienced amenorrhea and hot flushes. The patient was diagnosed with chemotherapy-induced early menopause.
99mTc-MDP Bone Scan Findings of Recurrent Langerhans Cell Histiocytosis in an Adult Involving Femur After Joint Replacement
Authors: Tingting Xu, Bing Cen, Hongmei Li, Yudi Wang, Yue Chen
Journal: Clinical Nuclear Medicine (2023)

Langerhans cell histiocytosis (LCH) is a rare proliferative histiocytic disorder. It mainly occurs in children and is rare in adults. We reported 99m Tc-MDP bone scan findings of recurrent LCH in an adult, which involved the right femur after right-side total hip arthroplasty. This case emphasizes that the possibility of LCH should be considered in osteolytic lesions in adults, especially after joint replacement. In addition, LCH should be included in the differential diagnosis of prosthetic joint pain and abnormal 3-phase bone scan after prosthesis arthroplasty.
Unexpected gastric perforation during endoscopic submucosal tunnel dissection for early circumferential esophageal cancer
Authors: Jingjing Lian, Aiping Xu, Tao Chen, Haibin Zhang, Meidong Xu
Journal: Endoscopy (2023)

Endoscopic submucosal dissection (ESD) has been widely accepted as an effective and minimally invasive treatment for superficial esophageal neoplasms. Mallory–Weiss tear (MWT) during esophageal ESD has been recognized as a possible complication, with an approximate incidence of 5.4 % according to Chen et al. [1] Here, we report a very rare case in which Mallory–Weiss tear led to severe gastric perforation during esophageal ESD.
Coloenterostomy performed endoscopically using through-the-scope twin clips in a porcine model
Authors: Qiang Zhang, Zhen Wang, Chudi Chen, Side Liu
Journal: Endoscopy (2023)

A novel through-the-scope twin clip or dual action tissue closure device (TTS-TC or DAT Closure Device; Micro-Tech Co. Ltd., Nanjing, China) was first reported by us [1] [2]. We have previously performed endoscopic gastric bypass using TTS-TCs in a live pig [3]. We have now for the first time performed coloenterostomy, similarly to colonic–small intestinal bypass, in a live pig. The operation steps are shown in [Video 1].
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity
Authors: Sean Wharton, Thomas Blevins, Lisa Connery, Julio Rosenstock, Sohini Raha, Rong Liu, Xiaosu Ma, Kieren J. Mather, Axel Haupt, Deborah Robins, Edward Pratt, Christof Kazda, Manige Konig
Journal: New England Journal of Medicine (2023)

Obesity is a major risk factor for many leading causes of illness and death worldwide. Data are needed regarding the efficacy and safety of the nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron as a once-daily oral therapy for weight reduction in adults with obesity.In this phase 2, randomized, double-blind trial, we enrolled adults with obesity, or with overweight plus at least one weight-related coexisting condition, and without diabetes. Participants were randomly assigned to receive orforglipron at one of four doses (12, 24, 36, or 45 mg) or placebo once daily for 36 weeks. The percentage change from baseline in body weight was assessed at week 26 (primary end point) and at week 36 (secondary end point).A total of 272 participants underwent randomization. At baseline, the mean body weight was 108.7 kg, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 37.9. At week 26, the mean change from baseline in body weight ranged from -8.6% to -12.6% across the orforglipron dose cohorts and was -2.0% in the placebo group. At week 36, the mean change ranged from -9.4% to -14.7% with orforglipron and was -2.3% with placebo. A weight reduction of at least 10% by week 36 occurred in 46 to 75% of the participants who received orforglipron, as compared with 9% who received placebo. The use of orforglipron led to improvement in all prespecified weight-related and cardiometabolic measures. The most common adverse events reported with orforglipron were gastrointestinal events, which were mild to moderate, occurred primarily during dose escalation, and led to discontinuation of orforglipron in 10 to 17% of participants across dose cohorts. The safety profile of orforglipron was consistent with that of the GLP-1 receptor agonist class.Daily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists. (Funded by Eli Lilly; GZGI ClinicalTrials.gov number, NCT05051579.).
Associations of subcutaneous fat area and Systemic Immune-inflammation Index with survival in patients with advanced gastric cancer receiving dual PD-1 and HER2 blockade
Authors: Meng He, Zi-Fan Chen, Li Zhang, Xiangyu Gao, Xiaoyi Chong, Hao-shen Li, Lin Shen, Jiafu Ji, Xiaotian Zhang, Bin Dong, Zi-Yu Li, Tang Lei
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Systemic Immune-inflammation Index (SII) and body composition parameters are easily assessed, and can predict overall survival (OS) in various cancers, allowing early intervention. This study aimed to assess the correlation between CT-derived body composition parameters and SII and OS in patients with advanced gastric cancer receiving dual programmed death-1 (PD-1) and human epidermal growth factor receptor 2 (HER2) blockade. Materials and methods This retrospective study enrolled patients with advanced gastric cancer treated with dual PD-1 and HER2 blockade from March 2019 to June 2022. We developed a deep learning model based on nnU-Net to automatically segment skeletal muscle, subcutaneous fat and visceral fat at the third lumbar level, and calculated the corresponding Skeletal Muscle Index, skeletal muscle density, subcutaneous fat area (SFA) and visceral fat area. SII was computed using the formula that total peripheral platelet count×neutrophil/lymphocyte ratio. Univariate and multivariate Cox regression analysis were used to determine the associations between SII, body composition parameters and OS. Results The automatic segmentation deep learning model was developed to efficiently segment body composition in 158 patients (0.23 s/image). Multivariate Cox analysis revealed that high SII (HR=2.49 (95% CI 1.54 to 4.01), p&lt;0.001) and high SFA (HR=0.42 (95% CI 0.24 to 0.73), p=0.002) were independently associated with OS, whereas sarcopenia was not an independent prognostic factor for OS (HR=1.41 (95% CI 0.86 to 2.31), p=0.173). In further analysis, patients with high SII and low SFA had worse long-term prognosis compared with those with low SII and high SFA (HR=8.19 (95% CI 3.91 to 17.16), p&lt;0.001). Conclusion Pretreatment SFA and SII were significantly associated with OS in patients with advanced gastric cancer. A comprehensive analysis of SII and SFA may improve the prognostic stratification of patients with gastric cancer receiving dual PD-1 and HER2 blockade.
Association between migration and severe maternal outcomes in high-income countries: Systematic review and meta-analysis
Authors: Maxime Eslier, Elie Azria, Konstantinos Chatzistergiou, Zelda Stewart, Agnès Dechartres, Catherine Deneux-Tharaux
Journal: PLoS Medicine (2023)

Background Literature focusing on migration and maternal health inequalities is inconclusive, possibly because of the heterogeneous definitions and settings studied. We aimed to synthesize the literature comparing the risks of severe maternal outcomes in high-income countries between migrant and native-born women, overall and by host country and region of birth. Methods and findings Systematic literature review and meta-analysis using the Medline/PubMed, Embase, and Cochrane Library databases for the period from January 1, 1990 to April 18, 2023. We included observational studies comparing the risk of maternal mortality or all-cause or cause-specific severe maternal morbidity in high-income countries between migrant women, defined by birth outside the host country, and native-born women; used the Newcastle–Ottawa scale tool to assess risk of bias; and performed random-effects meta-analyses. Subgroup analyses were planned by host country and region of birth. The initial 2,290 unique references produced 35 studies published as 39 reports covering Europe, Australia, the United States of America, and Canada. In Europe, migrant women had a higher risk of maternal mortality than native-born women (pooled risk ratio [RR], 1.34; 95% confidence interval [CI], 1.14, 1.58; p &lt; 0.001), but not in the USA or Australia. Some subgroups of migrant women, including those born in sub-Saharan Africa (pooled RR, 2.91; 95% CI, 2.03, 4.15; p &lt; 0.001), Latin America and the Caribbean (pooled RR, 2.77; 95% CI, 1.43, 5.35; p = 0.002), and Asia (pooled RR, 1.57, 95% CI, 1.09, 2.26; p = 0.01) were at higher risk of maternal mortality than native-born women, but not those born in Europe or in the Middle East and North Africa. Although they were studied less often and with heterogeneous definitions of outcomes, patterns for all-cause severe maternal morbidity and maternal intensive care unit admission were similar. We were unable to take into account other social factors that might interact with migrant status to determine maternal health because many of these data were unavailable. Conclusions In this systematic review of the existing literature applying a single definition of “migrant” women, we found that the differential risk of severe maternal outcomes in migrant versus native-born women in high-income countries varied by host country and region of origin. These data highlight the need to further explore the mechanisms underlying these inequities. Trial Registration PROSPERO CRD42021224193 .